Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice
Abstract
We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.
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For some psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms and slow the progression of neurodegeneration, although these findings are equivocal with some studies reporting caffeine increases depressive symptoms.
“For some psychiatric illness, such as Parkinson’s disease, Alzheimer’s disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms (204, 205) and slow the progression of neurodegeneration (206, 207), although these findings are equivocal with some studies reporting caffeine increases depressive symptoms (208).”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [204]
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- Authors
- Arendash, G. W., Mori, T., Cao, C., Mamcarz, M., Runfeldt, M., Dickson, A., Rezai-Zadeh, K., Tan, J., Citron, B. A., Lin, X., Echeverria, V., & Potter, H.
- Affiliations
- University of South Florida (US)
- Social Insurance Saitama Chuo Hospital (JP)
- Department of Molecular Medicine, University of South Florida, Tampa, FL, USA
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2009-07-01
- Volume
- 17
- Issue
- 3
- Pages
- 661-680
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2128860352
- Cited by
- 308
- References
- 65
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 23 · 2023: 20 · 2022: 21 · 2021: 22 · 2020: 12 · 2019: 12 · 2018: 26 · 2017: 15 · 2016: 16 · 2015: 19 · 2014: 25 · 2013: 10 · 2012: 23
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
- Funders
- National Institute on Aging (P50AG025711)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- caffeine, Alzheimer's disease
- MeSH terms
- Age Factors, Alzheimer Disease, Central Nervous System Stimulants, Animals, Brain, Caffeine, Cell Line, Transformed, Cognition Disorders, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Transgenic, Models, Biological, Neurons, Psychomotor Performance, Gene Expression Regulation, Enzymologic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cyclic AMP-Dependent Protein Kinases, Maze Learning, Proto-Oncogene Proteins c-raf, Glycogen Synthase Kinase 3, Mice, Presenilin-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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